The proposed project represents an attempt to define the mechanism of the control of cardiac contractility by examining the role of cyclic AMP-dependent protein kinase. This objective will be approached as follows: 1. Verify and characterize the effect of cyclic AMP-dependent protein kinase-catalyzed phosphorylation to enhance calcium uptake by cardiac sarcoplasmic reticulum. A purified protein kinase preparation will be obtained and used in these studies. 2. Determine the role of other enzymes in the cyclic AMP-dependent protein kinase catalyzed stimulation of calcium uptake by sarcoplasmic reticulum. Other enzymes to be studied are adenylate cyclase, phosphodiesterase, phosphoprotein phosphatase, and Ca ions-activated ATPase. 3. Compare effect of cyclic AMP-dependent protein kinase on calcium movements in cardiac sarcoplasmic reticulum with its effect on calcium movements in other cellular membranes and relate findings to the physiology of the intact muscle. Membranes to be compared are sarcoplasmic reticulum of slow and fast skeletal muscle, and cardiac sarcolemma. These studies should result in an understanding of some of the basic defects in cardiac disease and in the selection of a proper course of treatment and prevention.